N-Acetylcysteine prevents baker's-yeast-induced inflammation and fever.

OBJECTIVE AND DESIGN: To investigate whether N-acetylcysteine (NAC) alters baker's-yeast-induced fever and inflammation. MATERIAL OR SUBJECTS: Male Wistar rats (26-28 days old) injected with baker's yeast (135 mg/kg, intraperitoneal) or prostaglandin E(2) (300 ng/100 µL, intrathecal). TREATMENT: Rats were injected with NAC (500 mg/kg, subcutaneous, or 50 µg/100 µL, intrathecal) 1 h before, or 2 h after, pyrogen injection. METHODS: Rectal temperature changes induced by baker's yeast, PGE(2) and NAC were followed up over time. Four hours after baker's yeast injection, total leukocytes, protein, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and nonprotein thiol content were assessed in peritoneal lavage and hypothalamus. RESULTS: Systemic administration of NAC decreased leukocytes, protein, IL-1ß and TNF-α levels in peritoneal lavage, and decreased IL-1ß levels in the hypothalamus. The central administration of NAC prevented baker's-yeast-induced fever, but did not alter the febrile response elicited by prostaglandin E(2). CONCLUSION: These results suggest an anti-inflammatory and antipyretic role for NAC in yeast-induced peritonitis.

Diacerein decreases TNF-alpha and IL-1beta levels in peritoneal fluid and prevents Baker's yeast-induced fever in young rats.

OBJECTIVE: To investigate the effect of diacerein, an anti-inflammatory drug, on body temperature and protocols of fever induction in male Wistar rats. METHODS: The effect of diacerein (5.0 mg/kg, s.c.) on rectal temperature (T (R)) changes induced by Baker's yeast (0.135 g/kg, i.p.) and PGE(2) (10 ng/animal, i.t.) was evaluated. T (R) changes were recorded over time. The leukocyte count and TNF-alpha and IL-1beta content were evaluated in the peritoneal fluid by means of optical microscopy and enzyme immunoassay (ELISA kits), respectively. RESULTS: The administration of diacerein to febrile animals attenuated Baker's yeast-induced fever but did not alter prostaglandin E(2)-induced fever. Diacerein prevented the development of Baker's yeast-induced fever and significantly attenuated the increase in peritoneal leukocytes and decreased IL-1beta and TNF-alpha levels in peritoneal fluid. CONCLUSIONS: These data suggest that diacerein partially protects against Baker's yeast-induced fever and peritoneal leukocyte migration, and indicate that this effect appears to be due to inhibition of release of cytokines (such as TNF-alpha and IL-1beta).

Triterpene 3ß, 6ß, 16ß trihidroxilup-20(29)-ene protects against excitability and oxidative damage induced by pentylenetetrazol: the role of Na(+),K(+)-ATPase activity.

Administration of the compound triterpene 3ß, 6ß, 16ß-trihidroxilup-20(29)-ene (TTHL) resulted in antinociceptive activity in several pain models in mice. Because pain and epilepsy have common mechanisms, and several anticonvulsants are clinically used to treat painful disorders, we investigated the anticonvulsant potential of TTHL. Behavioral and electrographic recordings revealed that pretreatment with TTHL (30 mg/kg; i.g.) increased the latencies to the first clonic seizure to the tonic-clonic and reduced the duration of the generalized seizures induced by the GABA(A) receptor antagonist PTZ (80 g; i.p.). The TTHL pretreatment also protected against PTZ-induced deleterious effects, as characterized by protein carbonylation, lipid peroxidation, [(3)H] glutamate uptake and the inhibition of Na(+),K(+)-ATPase (subunits α(1) and α(2)/α(3)). Although TTHL did not exhibit DPPH, ABTS radical scavenging activity per se and does not alter the binding of [(3)H]flunitrazepam to the benzodiazepinic site of the GABA(A) receptor, this compound was effective in preventing behavioral and EEG seizures, as well as the inhibition of Na(+),K(+)-ATPase induced by ouabain. These results suggest that the protection against PTZ-induced seizures elicited by TTHL is due to Na(+),K(+)-ATPase activity maintenance. In fact, experiments in homogenates of the cerebral cortex revealed that PTZ (10 mM) reduced Na(+),K(+)-ATPase activity and that previous incubation with TTHL (10 µM) protected against this inhibition. Collectively, these data indicate that the protection exerted by TTHL in this model of convulsion is not related to antioxidant activity or GABAergic activity. However, these results demonstrated that the effective protection of Na(+),K(+)-ATPase elicited by this compound protects against the damage due to neuronal excitability and oxidation that is induced by PTZ.

Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury.

Achievements made over the last years have highlighted the important role of creatine in health and disease. However, its effects on hyperexcitable circuit and oxidative damage induced by traumatic brain injury (TBI) are not well understood. In the present study we revealed that severe TBI elicited by fluid percussion brain injury induced oxidative damage characterized by protein carbonylation, thiobarbituric acid reactive species (TBARS) increase and Na(+),K(+)-ATPase activity inhibition 4 and 8 days after neuronal injury. Statistical analysis showed that after TBI creatine supplementation (300 mg/kg, p.o.) decreased the levels of protein carbonyl and TBARS but did not protect against TBI-induced Na(+),K(+)-ATPase activity inhibition. Electroencephalography (EEG) analysis revealed that the injection of a subconvulsant dose of PTZ (35 mg/kg, i.p.), 4 but not 8 days after neuronal injury, decreased latency for the first clonic seizures and increased the time of spent generalized tonic-clonic seizures compared with the sham group. In addition, creatine supplementation had no effect on convulsive parameters induced by a subconvulsant dose of PTZ. Current experiments provide evidence that lipid and protein oxidation represents a separate pathway in the early post-traumatic seizures susceptibility. Furthermore, the lack of consistent anticonvulsant effect exerted by creatine in this early phase suggests that its apparent antioxidant effect does not protect against excitatory input generation induced by TBI.